The applicant proposes to measure changes in the size and number of neurons and their dendrites and axons in the TThC in his transgenic mice. To determine the mechanisms by which IGF-I influences neural development, he will examine IGF-I's in vivo effects on a) neuronal cell proliferation and migration, b) neuronal apoptosis, c) the regulation of type I receptors and d) the expression of candidate genes that may mediate the changes induced by IGF-I. The modulatory effects of IGFBPs will also be studied using primary neuronal studies. Finally, the applicant will test the hypothesis that decreases in IGF-I expression or actions mediate the brain pathology of malnutrition. He predicts that IGF-I overexpression will ameliorate and IGFBP-1 expression will exacerbate malnutrition's effects on the TThC.